Phlebitis treatment gel containing coptis chinensis-wine-treated rhubarb compound component and preparation method of phlebitis treatment gel

Abstract

The invention discloses a phlebitis treatment gel containing a coptis chinensis-wine-treated rhubarb compound component and a preparation method of the phlebitis treatment gel. The active ingredients of the gel are coptis chinensis, rheum officinale and wine-treated rheum officinale in a mass ratio of (1.5-2.5): (1.5-2.5): 1, preferably 2: 2: 1. Lavender essential oil, tea tree essential oil, folium eucalypti essential oil and vinegar frankincense, radix trichosanthis and other traditional Chinese medicine auxiliary materials are used as auxiliary materials. The preparation method comprises the following steps: extracting twice with ethanol, mixing extracting solutions, adding borneol, menthol and essential oil, and finally gelling with carbomer. The phlebitis gel can be independently used or combined with indometacin to form dual-channel anti-inflammation, and the defects of skin atrophy, toxicity accumulation and the like of traditional phlebitis gel are overcome. The traditional Chinese medicine composition is clinically expanded and applied to first-stage pressure sores (without skin damage), acnes and mosquito bites, red and swollen of the first-stage pressure sores fade away within 3-5 days, red and swollen of the acnes are relieved by more than or equal to 60% when the traditional Chinese medicine composition is combined with oral medicine for 48 hours, the itching relieving effect on the mosquito bites is less than or equal to 30 minutes, and the curative effect on phlebitis is remarkably superior to that of 50% magnesium sulfate (Plt;

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine gels, and specifically discloses a phlebitis treatment gel containing a compound of Coptis chinensis and rhubarb, and its preparation method. Background Technology

[0002] While some commercially available phlebitis gels may be effective, they can cause the following problems; 1. Skin atrophy Some unregulated or "purely herbal" phlebitis gels may illegally contain corticosteroids (such as dexamethasone and betamethasone), which are difficult for users to identify from the ingredient list. Long-term use can easily lead to skin atrophy. Skin atrophy refers to a reduction in the volume and thickness of skin tissue, which may cause the skin to become fragile and sensitive, further aggravating skin problems.

[0003] 2. Increased skin fragility In the use of traditional Chinese medicine phlebitis gel, some products contain irritating Chinese herbs (such as chili peppers, Sichuan peppercorns, and inappropriate amounts of menthol), photosensitive ingredients (such as psoralea corylifolia, angelica dahurica, and angelica pubescens), or extracts that are prone to causing allergies (such as extracts of safflower, chuanxiong, and notoginseng). These ingredients may damage the skin barrier, leading to increased skin fragility (such as dryness, sensitivity, and easy damage), making the skin more susceptible to external stimuli and exacerbating inflammatory reactions.

[0004] 3. Some traditional Chinese medicine gels may contain toxic components (such as aconite and cassia bark that have not been properly processed, which contain aconitine) or heavy metals (such as arsenic in realgar), which may accumulate locally after transdermal absorption. When the skin is broken, the absorption of toxic components increases, which may cause local tissue necrosis or nerve damage. Long-term use of gels containing toxic components may lead to local skin pigmentation, hardening, or even changes similar to "scleroderma".

[0005] 4. Traditional Chinese medicine ingredients may dissolve lipids in the stratum corneum or affect the expression of skin barrier-related proteins (such as filaggrin), leading to increased transepidermal water loss (TEWL). Improper use of transdermal absorption enhancers (such as azone) may excessively damage the stratum corneum structure, making the skin sensitive, dry, and susceptible to external stimuli (such as friction, cold, and heat), and may induce or aggravate itching and inflammatory reactions associated with phlebitis.

[0006] 5. Existing medications for treating skin inflammation (such as silver sulfadiazine cream for pressure sores, tretinoin for acne, and steroid creams for insect bites) have problems such as drug resistance, skin irritation, or steroid dependence. Furthermore, the 50% magnesium sulfate wet compress commonly used in the treatment of phlebitis has a slow onset of action (requiring 5-10 days), is inconvenient to use, and has limited effect on softening induration. Summary of the Invention

[0007] To address the above problems, this invention provides a phlebitis treatment gel containing a compound of Coptis chinensis and rhubarb, and its preparation method.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for preparing a phlebitis treatment gel containing a compound of Coptis chinensis and rhubarb (processed with wine), comprising the following steps: (a) Weigh out the active ingredients according to the mass ratio of Coptis chinensis: Rheum palmatum: Rheum palmatum (processed with wine) = (1.5–2.5):(1.5–2.5):1; (b) Mix the active ingredient with the excipient medicinal materials, add 5–7 times the mass of 65–75% ethanol and soak for 25–35 minutes, then decoct for 40–50 minutes to obtain the first extract; (c) Add 3–5 times the mass of 65–75% ethanol to the residue and decoct for 25–35 minutes to obtain the second extract; (d) Combine the two extracts, add borneol and menthol, and heat to dissolve; (e) Add 0.02–0.1 wt% lavender essential oil, 0.02–0.1 wt% tea tree essential oil, and 0.05–0.2 wt% eucalyptus essential oil and stir to mix; (f) Add carbomer and triethanolamine to prepare a gel matrix.

[0009] Furthermore, the above preparation method, The mass ratio of the active ingredients in step (b) is Coptis chinensis: Rheum palmatum: Rheum palmatum (processed with wine) = 2:2:1. Step (b) involves adding 6 times the mass of ethanol at a 70% concentration, soaking for 30 minutes, and then decocting for 45 minutes. Step (c) Add 4 times the mass of ethanol, 70% concentration, and decoct for 30 minutes.

[0010] Furthermore, in the above preparation method, the excipients in step (b) include vinegar-processed frankincense, trichosanthes root, pearl powder, licorice, fritillaria cirrhosa, vinegar-processed myrrh, and calcined dragon bone. Its mass ratio is: vinegar-processed frankincense: trichosanthes root: pearl powder: licorice: fritillaria cirrhosa: vinegar-processed myrrh: calcined dragon bone = 2:2:1:1:3:2:3.

[0011] Furthermore, in the above preparation method, the amount of essential oil added in step (e) is 0.046 wt% lavender essential oil, 0.046 wt% tea tree essential oil, and 0.09 wt% eucalyptus essential oil.

[0012] Furthermore, in the above preparation method, the amount of carbomer added in step (f) is 1–1.5% of the total mass of the gel.

[0013] This invention discloses a phlebitis treatment gel containing a compound of Coptis chinensis and rhubarb, which is prepared by the above method.

[0014] The present invention also discloses the application of the above-mentioned gel in the preparation of a drug for treating grade III phlebitis.

[0015] This invention also discloses the application of the gel in the preparation of a drug for treating grade III phlebitis in combination with indomethacin.

[0016] Furthermore, the present invention also discloses a pharmaceutical combination package for treating phlebitis, comprising the above-mentioned gel and indomethacin ointment.

[0017] The present invention also discloses the application of the above-mentioned gel in the preparation of a medicament for treating inflammatory skin diseases, including phlebitis, stage I pressure ulcers (without skin breakage), acne, or redness, swelling, and itching caused by insect bites; in: When treating phlebitis, it takes 3-7 days for the induration to shrink by ≥50%. When treating stage 1 pressure ulcers, it takes 3-5 days for the redness and swelling to subside; When treating acne, combined use of oral antibiotics resulted in a ≥60% reduction in redness and swelling within 48 hours. When treating mosquito bites, the time for relieving itching is ≤30 minutes.

[0018] Furthermore, in the above applications, when used to treat phlebitis or stage I pressure ulcers, the combination with indomethacin forms a dual-pathway anti-inflammatory effect, with the efficacy for phlebitis being superior to that of 50% magnesium sulfate wet compresses (P<0.05).

[0019] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention significantly improves the therapeutic effect of phlebitis by optimizing the compound ratio of Coptis chinensis and rhubarb (2:2:1) and the ethanol gradient extraction process, combined with a specific essential oil combination: 2. Powerful anti-inflammatory and blood-activating effects: Double the amount of Coptis chinensis and rhubarb enhances heat-clearing and detoxifying properties, while wine-processed rhubarb promotes microcirculation, quickly eliminating redness, swelling, and pain (effective within 24–48 hours), with an efficacy rate of nearly 90% in softening grade III phlebitis induration; 3. Safety breakthrough: It excludes glucocorticoids, toxic Chinese herbal medicines and photosensitizing ingredients. The essential oil blend reduces transepidermal water loss (TEWL), repairs the skin barrier, and has a clinical dermatitis incidence rate of <5% with no risk of skin atrophy. 4. Synergistic and extended application: When used in combination with indomethacin, it forms a dual anti-inflammatory pathway of "inhibiting endotoxin + cyclooxygenase", which enhances efficacy while avoiding the side effects of Western medicine; 5. Process advantages: Two ethanol extractions fully preserve the active ingredients, and the addition of essential oils ensures stability, making it suitable for industrial production.

[0020] 6. Advantages of expanding indications: Stage 1 pressure ulcers: Through the effects of clearing heat and detoxifying, reducing swelling and relieving pain, redness and swelling subside in 3-5 days (compared to 7 days for silver sulfadiazine); Acne: Combined oral antibiotics (such as doxycycline) reduced redness and swelling by ≥60% within 48 hours and accelerated the resolution of papules and pustules; Mosquito bites: The essential oil components instantly soothe nerve endings and relieve itching within 30 minutes (faster than 45 minutes for steroid creams). Phlebitis: The therapeutic effect was significantly better than that of 50% magnesium sulfate wet compress (the induration reduction rate increased by 35%, P<0.05). Detailed Implementation

[0021] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] The raw materials used in the examples were all purchased through commercial channels and are traditional Chinese medicine decoction pieces that meet the standards of the National Pharmacopoeia.

[0023] Example 1 A method for preparing a phlebitis treatment gel containing a compound of Coptis chinensis and rhubarb. Raw material usage: Active ingredients: 150g Coptis chinensis, 150g Rheum palmatum, 100g Rheum palmatum (ratio 1.5:1.5:1) Excipients and medicinal materials: 200g of vinegar-processed frankincense, 200g of trichosanthes root, 100g of pearl powder, 100g of licorice root, 300g of fritillaria bulb, 200g of vinegar-processed myrrh, and 300g of calcined dragon bone (ratio 2:2:1:1:3:2:3). Preparation steps: (a) After mixing the medicinal materials, add 5 times the mass of 65% ethanol (total medicinal material mass = 150 + 150 + 100 + 200 + 200 + 100 + 100 + 300 + 200 + 300 = 1800g → ethanol amount = 5 × 1800 = 9000g), soak for 25 minutes, decoct for 40 minutes, and obtain the first extract; (b) Add 3 times the mass of 65% ethanol to the residue (3×1800=5400g), decoct for 25 minutes, and obtain the second extract; (c) Combine the extracts (approximately 12L), add 100g of borneol and 200g of menthol, and heat to dissolve; (d) Add 0.02wt% lavender essential oil (final gel weight is 1.0g based on 5000g), 0.02wt% tea tree essential oil (1.0g), and 0.05wt% eucalyptus essential oil (2.5g), and stir to mix; (e) Add 1.0 wt% (50 g) of carbomer and triethanolamine (2.5 times the amount of carbomer → 125 g) to make 5000 g of gel.

[0024] Example 2 A method for preparing a phlebitis treatment gel containing a compound of Coptis chinensis and rhubarb. Raw material usage: Active ingredients: 200g Coptis chinensis, 200g Rheum palmatum, 100g Rheum palmatum (ratio 2:2:1) Excipients and medicinal materials: 300g of vinegar-processed frankincense, 300g of trichosanthes root, 150g of pearl powder, 150g of licorice root, 450g of fritillaria bulb, 300g of vinegar-processed myrrh, and 450g of calcined dragon bone (ratio 2:2:1:1:3:2:3). Preparation steps: (a) After mixing the medicinal materials, add 6 times the mass of 70% ethanol (total medicinal material mass = 200 + 200 + 100 + 300 + 300 + 150 + 150 + 450 + 300 + 450 = 2500g → ethanol amount = 6 × 2500 = 15000g), soak for 30 minutes, decoct for 45 minutes, and obtain the first extract; (b) Add 4 times the mass of 70% ethanol to the residue (4×2500=10000g), decoct for 30 minutes, and obtain the second extract; (c) Combine the extracts (approximately 20L), add 150g of borneol and 300g of menthol, and heat to dissolve; (d) Add 0.046wt% lavender essential oil (final gel weight 8000g → 3.68g), 0.046wt% tea tree essential oil (3.68g), and 0.09wt% eucalyptus essential oil (7.2g), and stir to mix; (e) Add 1.2wt% (96g) of carbomer and triethanolamine (2.67 times that of carbomer → 256g) to make 8000g of gel.

[0025] Example 3 A method for preparing a phlebitis treatment gel containing a compound of Coptis chinensis and rhubarb. Raw material usage: Active ingredients: 250g Coptis chinensis, 250g Rheum palmatum, 100g Rheum palmatum (ratio 2.5:2.5:1) Excipients and medicinal materials: 400g of vinegar-processed frankincense, 400g of trichosanthes root, 200g of pearl powder, 200g of licorice root, 600g of fritillaria cirrhosa, 400g of vinegar-processed myrrh, and 600g of calcined dragon bone (ratio 2:2:1:1:3:2:3). Preparation steps: (a) After mixing the medicinal materials, add 7 times the mass of 75% ethanol (total medicinal material mass = 250 + 250 + 100 + 400 + 400 + 200 + 200 + 600 + 400 + 600 = 3400g → ethanol amount = 7 × 3400 = 23800g), soak for 35 minutes, decoct for 50 minutes, and obtain the first extract; (b) Add 5 times the mass of 75% ethanol to the residue (5×3400=17000g), decoct for 35 minutes, and obtain the second extract; (c) Combine the extracts (approximately 30L), add 200g of borneol and 400g of menthol, and heat to dissolve; (d) Add 0.1wt% lavender essential oil (final gel weight 10000g → 10.0g), 0.1wt% tea tree essential oil (10.0g), and 0.2wt% eucalyptus essential oil (20.0g), and stir to mix; (e) Add 1.5wt% (150g) of carbomer and triethanolamine (3 times the amount of carbomer → 450g) to make 10000g of gel.

[0026] Comparative Example 1 The ratio is out of range: 1:1:1 raw material: Active ingredients: 100g Coptis chinensis, 100g Rheum palmatum, 100g Rheum palmatum (ratio 1:1:1) Excipients and medicinal materials: Same as in Example 2 (300g of vinegar-processed frankincense, etc.) Steps: Same as in Example 2.

[0027] Comparative Example 2 Lacking rhubarb wine raw material: Active ingredients: Coptis chinensis 200g, Rheum palmatum 200g, Rheum palmatum (processed with wine) 0g Excipients and medicinal materials: Same as in Example 2 Steps: Same as in Example 2.

[0028] Comparative Example 3 Insufficient ethanol concentration Raw materials: Same as in Example 2 step: Steps (a) and (b) use 50% ethanol (Claim 1 requires 65-75%). The rest is the same as in Example 2.

[0029] Comparative Example 4 essential oil deficiency Raw materials: Same as in Example 2 Steps: Same as in Example 2, but without adding essential oils.

[0030] Comparative Example 5 Incorrect proportions of auxiliary materials raw material: Active ingredient: Same as in Example 2 Excipients and medicinal materials: 300g of vinegar-processed frankincense, 600g of trichosanthes root (originally 300g), 150g of pearl powder, 150g of licorice root, 450g of fritillaria cirrhosa, 300g of vinegar-processed myrrh, and 450g of calcined dragon bone (ratio changed to 2:4:1:1:3:2:3). Steps: Same as in Example 2.

[0031] Test Example 1 Comparative experiment on the inhibitory capacity of anti-inflammatory factors Objective: To verify the synergistic inhibitory effect of the optimal ratio (2:2:1) on the key inflammatory factors TNF-α and IL-6. method: Sample preparation: Take the gel extracts (equivalent to 1 g / mL of crude drug) from Example 2 (ratio 2:2:1), Comparative Example 1 (ratio 1:1:1), and Comparative Example 2 (rhubarb without alcohol). LPS-induced macrophage (RAW264.7) inflammation model: Cells were seeded in 6-well plates (1×10⁻⁶ cells / wells). 6 cells / well) Handling method: Blank group: culture medium only Model group: LPS 1 μg / mL stimulation Drug administration group: LPS stimulation was combined with gel extract (final concentration 100 μg / mL). Detection method: After 24 hours of culture, the supernatant was collected, and the levels of TNF-α and IL-6 were detected by ELISA (kit: R&D Systems). Inhibition rate calculation formula: (Model group concentration - Drug group concentration) / Model group concentration × 100%.

[0032] The results are shown in Table 1 below. Table 1 Comparison of the inhibitory capacity of anti-inflammatory factors

[0033] (*P<0.01 vs Comparative Example 1) Conclusion: The 2:2:1 ratio (Example 2) significantly improved the inhibition rate of anti-inflammatory factors (TNF-α inhibition rate was 66% higher than that of control Example 1). Rhubarb wine promoted the penetration of Coptis chinensis active ingredients by enhancing microcirculation and synergistically inhibited the NF-κB pathway.

[0034] Test Example 2 Clinical efficacy verification of grade III phlebitis method: Patient inclusion criteria: The patient was diagnosed with grade III phlebitis (INS classification criteria: palpable induration > 2.5 cm, accompanied by redness, swelling, heat and pain). Affected areas: superficial veins of the upper limb, forearm, or back of the hand (avoid interference from deep vein thrombosis). Exclusion criteria: Individuals with diabetes, skin ulcers, or immunodeficiency. Grouping and drug administration are shown in Table 2 (n=15 per group, randomized double-blind). Table 2 Grouping and Dosage

[0035] Frequency: 3 times daily (8:00 / 14:00 / 20:00), for 7 consecutive days. Procedure: Disinfect the affected area with alcohol before application. Apply the gel evenly with a sterile cotton swab and allow it to air dry. Measurement of hardening shrinkage rate: Tools: Vernier calipers (accuracy 0.02 mm) Measurement points: Mark the longest diameter (L) and the shortest vertical diameter (W) of the hardened nodule, and calculate the approximate area (S=L×W). Time points: Before treatment (D0), after treatment (D7) Calculation formula: Nodule shrinkage rate (%) = [ (S_D0 - S_D7) / S_D0 ] × 100% Validity criterion: A reduction rate of ≥50% is considered valid.

[0036] The results are shown in Table 3.

[0037] Table 3: Clinical efficacy verification of grade III phlebitis

[0038] (*P<0.05 vs Example 1 group) Conclusion: The 2:2:1 ratio (Example 2) showed the best softening effect on grade III phlebitis induration (reduction rate of 61.7%), and the blood-activating and collateral-clearing effects of rhubarb and the heat-clearing and detoxifying effects of Coptis chinensis were synergistically enhanced.

[0039] Skin safety and barrier function assessment.

[0040] Test Example 3 Objective: To verify the effects of essential oil components on reducing the incidence of dermatitis and repairing the skin barrier. method: Animal models: SD rats (180-220 g) were shaved on their backs and treated with 7.5% sodium lauryl sulfate (SLS) to induce skin damage. Group processing (n=10 per group): Model group: No treatment after SLS injury Example 2: Applying a gel containing essential oils Comparative Example 4: Applying oil-free gel Positive control group: Vaseline Testing indicators: Transepidermal water loss (TEWL): Measured using Tewameter® TM300 on days 0, 3, and 7. Histological scoring: HE staining to assess epidermal integrity (0-4 points) The results are shown in Table 4. Table 4 Skin Barrier Test

[0041] (*P<0.05 vs. 4 comparative groups) Conclusion: The combination of lavender / tea tree / eucalyptus essential oils significantly improved skin barrier function by reducing TEWL by 28.7% (repairing the lipid structure of the stratum corneum).

[0042] Test Example 4 Dual-pathway anti-inflammatory efficacy of indomethacin Objective: To verify the synergistic mechanism of the combined use of gel and indomethacin. method: Experimental Design: Rat model of phlebitis (femoral vein damaged by 20% sodium chloride solution) Grouping (n=8 per group): Model group: physiological saline Gel alone: ​​Example 2 gel Indomethacin monotherapy group: 1% indomethacin ointment Combined group: Example 2 gel + 1% indomethacin ointment All medications (gels, ointments) are applied topically to the skin surface of the area affected by the femoral vein injury.

[0043] In the combined group, the gel of Example 2 (dosage same as the gel alone group) was first applied to the same skin area. After it was slightly absorbed (e.g., 15-30 minutes), 1% indomethacin ointment (dosage same as the indomethacin alone group) was then applied.

[0044] Testing indicators: Serum inflammatory factors: ELISA detection of TNF-α and IL-6 Histopathology: HE staining to assess the number of neutrophil infiltrates The results are shown in Table 5. Table 5. Validation of Dual-Pathway Anti-inflammatory Effects

[0045] (*P<0.01 vs. single-use group) Conclusion: The combined use increased the inflammation suppression rate by 82.4%, and the inhibition of the endotoxin pathway by Coptis chinensis and the inhibition of the cyclooxygenase pathway by indomethacin complemented each other.

[0046] Test Example 5 Long-term skin safety studies Objective: To assess the risk of skin atrophy after 14 days of continuous use. method: Subjects (n=20 per group, healthy volunteers): Grouping: Example 2 gel group, hormone ointment group (0.1% hydrocortisone), blank group Apply to forearms three times daily for 14 days. Testing indicators: Skin atrophy: High-frequency ultrasound detection of epidermal thickness (Dermascan C) Collagen density: Two-photon microscopy detection of collagen signal intensity The results are shown in Table 6. Table 6. Long-term skin safety

[0047] (*P<0.01 vs Example 2 group) Conclusion: This product does not pose a risk of skin atrophy (thickness decreased by 18.7% in the hormone ointment group), and collagen density increased by 5.1%.

[0048] Test Example 6 Research on the mechanism of essential oil penetration enhancement Objective: To verify the enhancing effect of essential oils on the transdermal absorption of active ingredients. method: Franz diffusion cell experiment: Excised pig skin (0.8 mm thick) Receiving solution: pH 7.4 PBS Grouping: Example 2 (containing essential oil) Comparative Example 4 (without essential oils) Adding 3 H-labeled berberine (Coptis chinensis marker) Detection: HPLC-MS determination of 24-hour cumulative permeability Observation of skin layer distribution using laser confocal microscopy The results are shown in Table 7. Table 7. Penetration-enhancing effects of essential oils

[0049] (*P<0.01) Conclusion: The essential oil increased the penetration of Coptis chinensis active ingredients by 212% and promoted enrichment in the dermis by opening hair follicle channels.

[0050] Test Example 7 Extended testing: It should be noted that this gel has been clinically validated and can be used for: (1) Stage 1 pressure ulcers (without breakage): After applying the ointment 3 times a day, the redness and swelling subsided in 3-5 days with a rate of 92.3% (n=40). (2) Inflammatory acne: Combined oral doxycycline (100mg / d), the area of ​​papules and swelling decreased by 62.5%±8.7% in 48 hours (n=35); (3) Insect bites: The VAS score for itching decreased by ≥4 points within 30 minutes after a single application (n=50); In summary, this invention has verified the core advantages of the phlebitis treatment gel through systematic test cases: 1. Anti-inflammatory synergy (Test Example 1): The 2:2:1 ratio significantly improved the inhibition rate of TNF-α / IL-6 (68.5% / 63.7%), which was 66% more effective than the non-optimal ratio (Comparative Example 1). The wine-processed rhubarb enhanced the penetration of Coptis chinensis active ingredients by promoting microcirculation and synergistically inhibited the NF-κB pathway. 2. Clinical efficacy advantages (test case 2): After 7 days of treatment, the induration reduction rate of patients with grade III phlebitis was 61.7% (effective rate 89.1%), and the pain was relieved rapidly within 24–48 hours. The efficacy was significantly better than that of petroleum jelly-based dressing (effective rate 65.0%). 3. Skin barrier repair (test case 3): The combination of lavender / tea tree / eucalyptus essential oils reduced transepidermal water loss (TEWL) by 28.7%, repaired the lipid structure of the stratum corneum, and the incidence of dermatitis was <5% (18.3% in the group without essential oils). 4. Synergistic effect of combined drug use (test case 4): When used in combination with indomethacin, it forms a dual anti-inflammatory pathway of "endotoxin inhibition + cyclooxygenase blockade", increasing the inhibition rate of inflammatory factors to 82.4%; 5. Long-term safety (Test Case 5): No skin atrophy (epidermal thickness +0.3%) was observed after 14 days of continuous use, while the atrophy rate in the hormone ointment group was >18%; 6. Penetration-enhancing mechanism (Test Example 6): The essential oil increased the transdermal absorption of Coptis chinensis active ingredients by 212%, and the concentration in the dermis was 2.8 times that in the epidermis.

[0051] In summary, this gel overcomes the shortcomings of traditional phlebitis gels, such as skin toxicity, slow onset of action, and difficulty in softening induration, through optimized formulation, process innovation, and component synergy, and combines high efficiency and safety.

[0052] The above are merely a few preferred embodiments of the present invention, described in a relatively specific and detailed manner, but they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

1. A method for preparing a phlebitis treatment gel containing a compound of Coptis chinensis and rhubarb, characterized in that, Includes the following steps: (a) Weigh out the active ingredients according to the mass ratio of Coptis chinensis: Rheum palmatum: Rheum palmatum (processed with wine) = (1.5–2.5):(1.5–2.5):1; (b) Mix the active ingredient with the excipient medicinal materials, add 5–7 times the mass of 65–75% ethanol and soak for 25–35 minutes, then decoct for 40–50 minutes to obtain the first extract; (c) Add 3–5 times the mass of 65–75% ethanol to the residue and decoct for 25–35 minutes to obtain the second extract; (d) Combine the two extracts, add borneol and menthol, and heat to dissolve; (e) Add 0.02–0.1 wt% lavender essential oil, 0.02–0.1 wt% tea tree essential oil, and 0.05–0.2 wt% eucalyptus essential oil and stir to mix; (f) Add carbomer and triethanolamine to prepare a gel matrix.

2. The preparation method according to claim 1, characterized in that: The mass ratio of the active ingredients in step (b) is Coptis chinensis: Rheum palmatum: Rheum palmatum (processed with wine) = 2:2:

1. Step (b) involves adding 6 times the mass of ethanol at a 70% concentration, soaking for 30 minutes, and then decocting for 45 minutes. Step (c) Add 4 times the mass of ethanol, 70% concentration, and decoct for 30 minutes.

3. The preparation method according to claim 1, characterized in that: The excipients mentioned in step (b) include vinegar-processed frankincense, trichosanthes root, pearl powder, licorice root, fritillaria bulb, vinegar-processed myrrh, and calcined dragon bone. Its mass ratio is: vinegar-processed frankincense: trichosanthes root: pearl powder: licorice: fritillaria cirrhosa: vinegar-processed myrrh: calcined dragon bone = 2:2:1:1:3:2:

3.

4. The preparation method according to claim 1, characterized in that: The essential oils added in step (e) are 0.046 wt% lavender essential oil, 0.046 wt% tea tree essential oil, and 0.09 wt% eucalyptus essential oil.

5. The preparation method according to claim 1, characterized in that, In step (f), the amount of carbomer added is 1–1.5% of the total mass of the gel.

6. A phlebitis treatment gel containing a compound of Coptis chinensis and rhubarb, characterized in that, Prepared by the method described in any one of claims 1-5.

7. The use of the gel as described in claim 6 in the preparation of a medicament for treating grade III phlebitis in combination with indomethacin.

8. A pharmaceutical combination package for treating phlebitis, comprising the gel of claim 6 and indomethacin ointment.

9. The use of the gel as described in claim 6 in the preparation of a medicament for treating inflammatory skin diseases, characterized in that: The inflammatory skin conditions mentioned include phlebitis, stage 1 pressure ulcers (without skin breakage), acne, or redness and itching caused by insect bites; in: When treating phlebitis, it takes 3-7 days for the induration to shrink by ≥50%. When treating stage 1 pressure ulcers, it takes 3-5 days for the redness and swelling to subside; When treating acne, combined use of oral antibiotics resulted in a ≥60% reduction in redness and swelling within 48 hours. When treating mosquito bites, the time for relieving itching is ≤30 minutes.

10. The application according to claim 9, characterized in that, When used in combination with indomethacin to treat phlebitis or stage 1 pressure ulcers, it forms a dual-pathway anti-inflammatory effect, with the efficacy of phlebitis treatment being superior to that of 50% magnesium sulfate wet compresses (P<0.05).

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